Abstract

Background

Transposable elements (TEs) encode sequences necessary for their own transposition,
including signals required for the termination of transcription. TE sequences within
the introns of human genes show an antisense orientation bias, which has been proposed
to reflect selection against TE sequences in the sense orientation owing to their
ability to terminate the transcription of host gene transcripts. While there is evidence
in support of this model for some elements, the extent to which TE sequences actually
terminate transcription of human gene across the genome remains an open question.

Results

Using high-throughput sequencing data, we have characterized over 9,000 distinct TE-derived
sequences that provide transcription termination sites for 5,747 human genes across
eight different cell types. Rarefaction curve analysis suggests that there may be
twice as many TE-derived termination sites (TE-TTS) genome-wide among all human cell
types. The local chromatin environment for these TE-TTS is similar to that seen for
3′ UTR canonical TTS and distinct from the chromatin environment of other intragenic
TE sequences. However, those TE-TTS located within the introns of human genes were
found to be far more cell type-specific than the canonical TTS. TE-TTS were much more
likely to be found in the sense orientation than other intragenic TE sequences of
the same TE family and TE-TTS in the sense orientation terminate transcription more
efficiently than those found in the antisense orientation. Alu sequences were found
to provide a large number of relatively weak TTS, whereas LTR elements provided a
smaller number of much stronger TTS.

Conclusions

TE sequences provide numerous termination sites to human genes, and TE-derived TTS
are particularly cell type-specific. Thus, TE sequences provide a powerful mechanism
for the diversification of transcriptional profiles between cell types and among evolutionary
lineages, since most TE-TTS are evolutionarily young. The extent of transcription
termination by TEs seen here, along with the preference for sense-oriented TE insertions
to provide TTS, is consistent with the observed antisense orientation bias of human
TEs.